Structural and functional characterization of a novel type of ligand-independent RXR-USP receptor.
Fiche publication
Date publication
août 2007
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MORAS Dino, Dr BILLAS Isabelle
Tous les auteurs :
Iwema T, Billas IM, Beck Y, Bonneton F, Nierengarten H, Chaumot A, Richards G, Laudet V, Moras D
Lien Pubmed
Résumé
Retinoid X receptor (RXR) and Ultraspiracle (USP) play a central role as ubiquitous heterodimerization partners of many nuclear receptors. While it has long been accepted that a wide range of ligands can activate vertebrate/mollusc RXRs, the existence and necessity of specific endogenous ligands activating RXR-USP in vivo is still matter of intense debate. Here we report the existence of a novel type of RXR-USP with a ligand-independent functional conformation. Our studies involved Tribolium USP (TcUSP) as representative of most arthropod RXR-USPs, with high sequence homology to vertebrate/mollusc RXRs. The crystal structure of the ligand-binding domain of TcUSP was solved in the context of the functional heterodimer with the ecdysone receptor (EcR). While EcR exhibits a canonical ligand-bound conformation, USP adopts an original apo structure. Our functional data demonstrate that TcUSP is a constitutively silent partner of EcR, and that none of the RXR ligands can bind and activate TcUSP. These findings together with a phylogenetic analysis suggest that RXR-USPs have undergone remarkable functional shifts during evolution and give insight into receptor-ligand binding evolution and dynamics.
Référence
EMBO J. 2007 Aug 22;26(16):3770-82